tbuckley/cabot-search huggingface dataset:
Efficacy of ovarian function suppression of 3-monthly versus monthly GnRH agonist as endocrine therapy for premenopausal breast cancer patients.
Authors: Daniella Audi Blotta, Jessica Ribeiro Gomes, Shermann Brandão Rodrigues Moreira, Danielle Fortes Colosimo, Carolina Cavalcanti Gonçalves Ferreira, Elaine Aparecida Forgiarini, Debora De Melo Gagliato, Antonio C. Buzaid
Journal: Journal of Clinical Oncology (2023)

527 Background: The combined analysis of the Suppression of Ovarian Function Trial (SOFT) and Tamoxifen and Exemestane Trial (TEXT) trials have shown significant survival benefit of adding ovarian function suppression (OFS) with GnRH agonists (GnRHa) to aromatase inhibitors (AI) versus tamoxifen in high-risk premenopausal patients (pts) with estrogen receptor (ER)-positive breast cancer (BC). In both studies, GnRHa was administered every 4 weeks. However, the efficacy of 3-monthly GnRHa plus AI has not been well studied. We conducted a retrospective study designed to assess the efficacy of OFS with 3-montlhy compared with monthly goserelin, associated with AI, in premenopausal pts with ER-positive BC. Methods: Medical records of premenopausal pts with ER-positive BC who received OFS with 10.8mg 3-montlhy goserelin plus AI or 3.6mg monthly goserelin plus AI, between June/2013 and January/2023 were reviewed. Patient characteristics, such as age, body mass index (BMI) and prior chemotherapy were analyzed. Estradiol (E2) levels were measured by gas chromatography tandem mass spectrometry. Pts with at least one E2 level above 2.72 pg/ml were considered to have ineffective OFS. Analysis of E2 measurements was divided into periods: &lt; 3, 3 to 6, 6 to 9, 9 to 12, 12 to 18, 18 to 24 and &gt; 24 months. E2 levels greater than 2.72 pg/ml were evaluated at each timepoint. Results: A total of 88 pts were included. 27 (30.7%) received monthly goserelin and 61 (69.3%) 3-monthly goserelin. Patient characteristics were well balanced between the groups. Relevant demographic data are shown in table. For E2 analysis, 20 (22.7%) pts had at least one measurement greater than 2.72 pg/ml, 11 (40.7%) in the monthly group and 9 (14.8%) in the 3-monthly group (p = 0.007). The percentages of E2 measurements ≥ 2.72 pg/ml, in each time period, were 0%, 40%, 12.5%, 16.7%, 33.3%, 50% and 50% in monthly group versus 8%, 4.2%, 10%, 14.3%, 4.8%, 8.3% and 5.6%, in 3-monthly group, respectively. Conclusions: Our study demonstrated that more pts who underwent 3-monthly goserelin had E2 levels below the defined threshold of 2.72 pg/ml compared with monthly goserelin, when associated with AI, with statistical significance. These findings suggest that 3-monthly goserelin may result in better efficacy in OFS when comparing with monthly and provide greater convenience for pts. [Table: see text]
Evolving adjuvant estrogen therapy prescribing among breast oncology workforce.
Authors: Kayla Polcari, Grace Keegan, Sarah Sharpe, Olwen Mary Hahn, Stacy Tessler Lindau, Ted Skolarus, Parth K. Modi, Sarah Shubeck
Journal: Journal of Clinical Oncology (2023)

1546 Background: An oncologist shortage and rising number of breast cancer survivors has created a strained workforce. Care models that incorporate advanced practice providers (APPs) are recommended to meet this rising demand, particularly during survivorship. The objective of this study is to describe the evolving oncology workforce using anti-estrogen prescribing as a surrogate for breast cancer survivorship care. Methods: We used Medicare Part D Public Use Files to identify prescribers of anti-estrogen therapy from 2013 to 2020. We included medications primarily prescribed in the adjuvant setting for estrogen receptor positive breast cancer, including anastrozole, letrozole, exemestane, tamoxifen, raloxifene, fulvestrant, and toremifene. We assessed the volume of physician and APP prescribers and claims by provider type using descriptive statistics and logistic regression. Individual prescribers were included if they had more than 10 claims. Results: The overall number of anti-estrogen claims did not change significantly from 2013 to 2020, with an average of 3,224,361 annually. There was a significant increase in APP prescribers from 7,815 (8.6%) in 2013 to 12,961 (18.3%) in 2020. There was a reduction in physician prescribers by 24,815 (9.7%) over the same period with an overall net decrease of total prescribers of 19,669 (21.7%). The average annual claims per individual prescriber rose from 2013 to 2020 (Physicians: 2013: 37.5 to 2020: 45.2, p &lt; 0.001; APP: 2013: 28.2 to 2020: 37.0, p &lt; 0.001). The percentage of claims attributed to APP prescribers rose substantially from 6.6% in 2013 to 15.5% in 2020. This represents an increase from 220,000 prescriptions in 2013 to over 480,000 in 2020. Conclusions: Our results indicate an ongoing shift in the provider composition responsible for delivering breast cancer survivorship care. Over the time frame analyzed, there was no significant change in number of prescription claims annually, but an overall decrease in providers. Thus, the rise in APP prescribers is not driven by an increased prescribing volume, but rather seems to reflect an evolving surgical oncology workforce. This has significant implications for the future access to and delivery of timely high-quality cancer care.[Table: see text]
Use of an artificial intelligence (AI) –based pre-screening tool for patients with bladder cancer with fibroblast growth factor receptor (FGFR) alteration.
Authors: Guobang Shi, Yanfei Yu, Aodi Wang, Ye Liu, Xiaoliang Shi
Journal: Journal of Clinical Oncology (2023)

e13580 Background: Over 25% of urothelial carcinoma have actionable genetic alterations in FGFR. The clinical trial of the pan-FGFR inhibitor requires thousands of patients with FGFR alterations to be screened; however, the cost is prohibitively expensive. A deep learning model can help predict the occurrence of specific genetic alterations and effectively screen patients with FGFR actionable alterations in bladder cancer. Methods: The prediction model of FGFR oncogenic alterations was trained by using 440 H&amp;E-stained bladder cancer diagnostic slides (from 373 patients) from the OrigiMed Database and validated with 448 slides (from 376 patients) from the additional TCGA-BLCA dataset. The model employs an attention-based, weakly supervised learning method to identify tissue subregions most likely to have the mutations of FGFR1-4, so as to classify the entire slide. Every patch is assigned an attention score, which represents the corresponding contribution to slide classification. The slide-level aggregation rule of attention-based pooling computes a final attention score by weighted average. Results: The FGFR oncogenic alteration predictive AI (FGFRonaP) model was trained, validated and tested on the OrigiMed real-world cohort. The FGFRonaP model could identify patients with FGFR1-4 gene oncogenic aberration on the test set accurately (Precision = 60.0%, Recall = 69.2%, AUROC = 0.839). When the model was tested on the additional TCGA independent cohort, 11 negative samples were included mistakenly while 323 true negative slide and 19 true positive slides were identified correctly. The FGFRonaP model showed an acceptable classification precision (63.3%), much higher than the occurrence rate (26.9%) of FGFR oncogenic alterations, in spite of an imperfect AUROC (0.636) and recall (0.167). Conclusions: FGFRonaP is feasible to serve as an in-house or monocentric application to pre-screen the potential FGFR-altered patients. It could be useful and efficient in preliminary screening to reduce workloads of genetic testing, and thus help pharmaceutical companies improve the proportion of candidates with FGFR-alterations in all patients who undergo genetic testing and cut expensive costs for enrolling patients.
Different efficacy of pembrolizumab in overall survival between Asians and non-Asians with advanced cancers: A systematic review and meta-regression analysis.
Authors: Shang-Hsuan Peng, Ching-Hung Lin, I-Chun Chen, Ying-Chun Shen, Dwan-Ying Chang, Tom Wei-Wu Chen, Shu-Min Huang, Fu-Chang Hu, Yen-Shen Lu
Journal: Journal of Clinical Oncology (2023)

e13597 Background: Immune checkpoint inhibitors have revolutionized the treatment landscape of malignancy. However, disproportionate enrollment among different races/ethnicities in global trials placed the generalizability in doubt. This meta-analysis aimed to estimate the relative efficacy of pembrolizumab between Asians and non-Asians with advanced cancers. Methods: A systematic review was conducted in PubMed, Cochrane Library, Embase, and Web of Science. The meta-analysis included phase 3 randomized controlled trials investigating pembrolizumab in advanced cancers with available subgroup analysis for Asians and non-Asians. The experimental strategies involved monotherapy versus standard-of-care (SOC) or best supportive care, an add-on to SOC, and combined with multikinase inhibitor versus standard chemotherapy, regardless of the setting. The primary and secondary effect measures were the mean difference (MD) in the natural logarithm (i.e., log) of the hazard ratio (HR) for overall survival (OS) and progression-free survival (PFS) between the two subgroups [MD=log(HR Asians )−log(HR Non-Asians )=log(HR Asians /HR Non-Asians )]. We used the random-effects meta-analysis to calculate the pooled ratio of HRs (i.e., exp(MD)) and implemented a meta-regression analysis to identify significant covariates. The heterogeneity among the selected studies was evaluated using the Chi-squared Q test and the I 2 statistic. Results: A total of 17 and 11 trials were selected in the meta-analysis for OS and PFS, respectively. These trials reported available subgroup results on Asians and non-Asians (patient numbers 2,732 [25.49%] and 7,000 [65.32%] for OS; 1,438 [22.50%] and 4,129 [64.61%] for PFS). The pooled ratio of HRs for OS was 0.87 (95% confidence interval [CI], 0.76−0.99; p = 0.0391; Chi-squared Q test Χ 2 = 20.84, p = 0.29; I 2 = 23.9%), favoring Asians, and no significant difference was found in PFS (the pooled ratio of HRs 0.93; 95% CI, 0.82−1.07; p = 0.2391; Chi-squared Q test Χ 2 = 7.37, p = 0.77; I 2 ≈ 0%). Both linear meta-regression analyses revealed an open-label design as an important covariate accounting for the observed difference, favoring non-Asians (estimated ratios of HR, 1.6318 for OS [95% CI, 1.1442-2.3273]; 1.3429 for PFS [95% CI, 1.0007−1.8020]). The sensitivity analysis showed that the percentage of subsequent treatment or post-progression programmed cell death 1 (PD-1)/ligand 1 (PD-L1) inhibitors had no significant impact. Conclusions: Asians receiving pembrolizumab for advanced cancers may have a superior OS advantage than non-Asians. Although the results warranted further exploration, this meta-analysis provided insight into clinical research design.
Extracellular mechanical forces and ferroptosis in triple negative breast cancer (TNBC): Targeting of aurora kinase A (AURKA).
Authors: Jinyan Wang, Zhonghua Tao, Yizhao Xie, Ye Wang, Duancheng Guo, Bin Li, Jianing Cao, Xiaosu Qiao, Xichun Hu
Journal: Journal of Clinical Oncology (2023)

e13086 Background: The mechanics of tumor microenvironment, primarily induced by extracellular matrix (ECM), function to regulate cell biological behaviors. However, it is unclear if and how triple negative breast cancer (TNBC) cells adapt their biological characteristics to variable extracellular mechanical forces. Methods: TNBC tissues of different stiffness from patients were harvested for untargeted metabolomics to investigate the potential effects of mechanical forces on metabolism. TNBC cells were cultured within gels of different type I collagen (Col-I) densities, which were the major component of ECM, to simulate the effects of extracellular mechanical forces on cells. The metabolic changes of TNBC cells were also examined by using untargeted metabolomics. TNBC cells bathed in different Col-I densities were injected subcutaneously into the breast pad of nude mice. Ferroptosis indicators were evaluated between different groups of mechanical force both in vitro and in vivo. Real-time quantitative polymerase chain reaction (RT-qPCR) and western blot were carried out to examine the expression of ferroptosis-related genes and proteins between different groups of mechanical force. Results: Untargeted metabolomics studies showed significant differences in ferroptosis-related metabolites between TNBC tissues with different stiffness, which were also verified in TNBC cells subjected to different extracellular mechanical forces. In vitro experiment suggested that TNBC cells cultured within high Col-I density (strong extracellular forces) exhibited higher levels of lipid peroxidation, reactive oxygen accumulation, mitochondria membrane potential and iron concentration, and lower levels of total glutathione and reduced glutathione concentration, compared with low Col-I density (weak extracellular forces). In addition, mitochondria in high Col-I density group appeared to have volume decrease, fracture and fuzzy cristae. The above results indicated that extracellular mechanical force significantly induced ferroptosis in TNBC. RT-qPCR and western blot of ferroptosis-related genes and protein showed that both mRNA and protein levels of aurora kinase A (AURKA) were significantly decreased in TNBC cells with strong extracellular mechanical force. In addition, overexpression of AURKA inhibited ferroptosis caused by mechanical forces. Furthermore, this cause and effect among mechanical force, AURKA and ferroptosis was also evident in vivo experiments. Conclusions: Our data clarified the role of extracellular mechanical forces in TNBC and showed that the extracellular mechanical forces induced ferroptosis through decreasing the expression of AURKA.
Tailored axillary surgery (TAS) in patients with clinically node-positive breast cancer in the upfront surgery setting: A prospective, single-arm, multicenter trial.
Authors: Kaori Terata, Yasuaki Sagara, Tadahiko Shien, Takehiko Sakai, Shin Takayama, Dai Kitagawa, Tsuguo Iwatani, Takahiro Tsukioki, Mami Ogita, Naoko Sanuki, Masayuki Yoshida, Hitoshi Tsuda, Seiichiro Yamamoto, Hiroji Iwata
Journal: Journal of Clinical Oncology (2023)

TPS628 Background: Axillary lymph node dissection (ALND), which can induce lymphedema, has been omitted in clinically node-negative(cN0) patients with positive sentinel lymph nodes (SLNs) if they meet the eligibility criteria of ACOSOG Z0011. Furthermore, the omission of ALND has been attempted through targeted axillary dissection (TAD) in patients whose cN+ status converts to ycN0 after neoadjuvant chemotherapy. However, ALND remains the standard of care in patients with cN+ who undergo upfront surgery. The aims of this trial are to establish a surgical method of tailored axillary surgery (TAS), which combines TAD and SLN biopsy among patients with cN+ who undergo upfront surgery, and to determine the appropriate criteria for a Phase III TAS trial. Methods: We have planned a single-arm Phase II trial to confirm the feasibility and assess patient eligibility for TAS. A total of 300 patients will be enrolled from 33 study sites in Japan. The eligibility criteria are as follows: 1) histologically-proven invasive breast cancer, 2) upfront surgery is planned, 3) pathologically-diagnosed metastatic lymph node (cytology or core needle biopsy), 4) 1-3 LN metastases in level I by imaging, 5) cT1-3, and 6) females aged ≥18 and ≤74 years on the enrollment date. TAS involves removing marking lymph nodes by TAD (clip, wire, or tattoo) and SLNB, and ALND up to Level II are performed after TAS. These LNs are defined as non-TAS LNs. The primary endpoint is the non-TAS LNs positive rate. Clinicopathological factors (the number of suspected metastases by imaging, the number of metastases in LNs resected by TAS, tumor size, and invasive ductal/lobular carcinoma) are analyzed to predict the non-TAS LN metastasis rate (e.g., &lt; 10%). By using these clinicopathological factors, we determine the eligibility of TAS to omit ALND safely. The secondary endpoints are TAS LNs identification rate, labeled LNs identification rate, marked lymph node resection rate, arm edema incidence rate, and QOL (FACT-B, QuickDASH). After this feasibility study, we will conduct a phase III trial that omits ALND using TAS to investigate the regional recurrence rate.
Outpatient practice utilization for CAR-T and T cell engager in patients with lymphoma and multiple myeloma.
Authors: Radhika Bansal, Jonas Paludo, Andre De Menezes Silva Corraes, Spychalla Megan, Arushi Khurana, Paul Joseph Hampel, Urshila Durani, David Dingli, Suzanne R. Hayman, Prashant Kapoor, Yucai Wang, Moritz Binder, Taxiarchis Kourelis, Shaji Kumar, Rahma M. Warsame, Nabila Nora Bennani, Morie A. Gertz, Patrick B. Johnston, Stephen M. Ansell, Yi Lin
Journal: Journal of Clinical Oncology (2023)

1533 Background: FDA-approved chimeric antigen receptor T-cell (CAR-T) and bispecific T cell engager (TCE) therapy are most commonly managed inpatient. Here we report our experience with hospital-based outpatient (HBO) management of patients (pts) receiving FDA-approved CAR-T or TCE and a predictive model for increased risk of early hospitalization (≤3 days post CAR-T). Methods: We reviewed the outcomes of pts who received FDA-approved CAR-T (axi-cel, brexu-cel, ide-cel, cilta-cel) or TCE (teclistamab) in the HBO unit between 3/2021 and 1/2023 at Mayo Clinic, Rochester. Results: HBO is closely integrated with inpatient practice and includes the same specialty trained clinical team. It is the first point of contact 24/7 for pts and triage evaluations. CAR-T and TCE are given on HBO followed by monitoring per REMS and as clinically needed until admission criteria is met. Remote patient monitoring (RPM) tools were used as part of outpatient monitoring. Out of 169 CAR-T pts, 87 (51%) were dosed with new indication/products (follicular lymphoma, mantle cell lymphoma, myeloma). Among those, 80 (92%) pts were dosed outpatient, among whom 21 (27%) were never hospitalized. CRS and ICANS incidences were comparable to that reported in registration studies. Median time to first admission from CAR-T infusion was 1 day (range, 0-9), with 31% (n=18/59) of admissions after day 3 post infusion. The most common cause of hospitalization was fever (n=40, 59%). Median length of hospital stay was 4 days (range, 1-49). Median time to tocilizumab (n=45, 80%), steroid (n=1, 2%), escalation of oxygen support (n=7, 12%), vasopressor (n=2, 3%), ventilator (n=1, 2%), hemodialysis (n=1, 2%) and ICU transfer (n=3, 5%) was 1 day (range, 0-31) after first admission. Use of bridging therapy, elevated CRP and LDH were predictive of early admission (ROC AUC 0.62). Four pts received teclistamab on HBO and enrolled in RPM. Data from more pts will be reported at ASCO. Conclusions: Our expanded study in CAR-T and TCE confirms that HBO is feasible and that CAR-T and TCE can be safely dosed outpatient. Approximately 31% of pts were admitted after 3 days from CAR-T infusion, and 27% of our pts were never admitted. Variables associated with aggressive disease can predict early hospitalization in pts receiving FDA-approved CAR-T. Extension of HBO practice to TCE is feasible.[Table: see text]
Role of plasma circulating <i>HER2/EFTUD2</i> ratio in predicting pathological complete response (pCR) after neoadjuvant dual anti-HER2 therapy in HER2-positive breast cancer (HER2+ BC).
Authors: Jeffrey CH Chan, William CS Cho, James CH Chow, Kelvin K H Bao, Alex KC Leung, Michelle OY Szeto, Connie HM Ho, Harry HY Yiu
Journal: Journal of Clinical Oncology (2023)

e12592 Background: Achieving pCR following neoadjuvant chemo and anti-HER2 therapy is associated with a significantly better survival in HER2+ BC. There is currently a lack of a robust biomarker to predict pCR in HER2+ BC. Using EFTUD2 as chromosome 17 reference probe, circulating HER2/EFTUD2 plasma DNA copy number ratio (H-ratio) detected by droplet digital PCR (ddPCR) was shown to have high concordance with the tumor HER2 status. We aim to evaluate whether the change in H-ratio is associated with response to neoadjuvant dual anti-HER2 therapy. Methods: We prospectively recruited patients with HER2+ BC who received neoadjuvant taxane, trastuzumab and pertuzumab followed by radical surgery from May 2019 to April 2022. Serial plasma samples (n = 49) were collected at pre-treatment (Tpre), at 4th cycle (Tmid) and at completion of neoadjuvant treatment (Tpost). H-ratio was determined in each plasma sample using droplet ddPCR (QX200 ddPCR system, Bio-rad). H-ratio responders were defined as patients having a declining Tpost H-ratio, whereas patients having a rising or persistent Tpost H-ratio were defined as H-ratio non-responders. The relationship between pCR, H-ratio and various clinicopathological characteristics were evaluated by Spearman’s correlation, Fisher’s exact test and Wilcoxon signed-rank test. Results: Eighteen clinical stage II or III HER2+ BC patients with a median age of 56 years old (range 33 - 71) were included. The median H-ratio at Tpre, Tmid and Tpost were 1.27, 1.12 and 1.10, respectively. Higher Tpre H-ratio was significantly associated with larger tumor size (p = 0.004) and higher tumor grade (G1-2 vs G3; median H-ratio 1.15 vs 1.78; p = 0.024). Six patients (33.3%) were H-ratio responders. Ten (55.6%) of 18 patients achieved pCR after completion of neoadjuvant treatment. The pCR rate in H-ratio responders was significantly higher than the H-ratio non-responders (100% vs. 36.4%; p = 0.017). In predicting pCR, H-ratio response outperformed hormonal receptor (HR) negativity (HR- vs HR+; 72.7% vs 28.6%; p = 0.088) or high tumor grade (G1-2 vs G3; 66.7% vs 33.3%; p = 0.201). There was no association between pCR and Tpre/Tmid/Tpost H-ratio. With a median follow up of 22.8 months (range 8.2 - 41.8), there were no relapse or death. Conclusions: A high pre-treatment plasma circulating HER2/EFTUD2 ratio is associated with large tumor size and high tumor grade in HER2+ BC. The decline of HER2/EFTUD2 ratio after neoadjuvant dual anti-HER2 therapy predicts pCR, and may serve as a potential biomarker for treatment de-escalation.